In this week's episode, Blood editor Dr. James Griffin interviews Drs. Thomas Milne and Dominique Bonnet on their latest articles published in volume 147 issue 24 of Blood. Dr. Milne discusses how transcription factors simultaneously activate enhancers and connect them to their target genes in KMT2A-rearranged acute lymphoblastic leukemia. The binding of MYB, a key hematopoietic TF, is sufficient to drive novel enhancer activation, including initiating 3D contact with target promoters to drive ectopic expression of distal oncogenes. Continued MYB binding is required to maintain enhancer-promoter interactions, indicating that disruption of MYB is therapeutically tractable in multiple leukemias. Then, considering bone marrow vasculature, Dr. Bonnet discusses how the use of in vivo models to identify selective injury to sinusoidal endothelial cells caused by venetoclax-azacitidine, revealed a therapy-associated mechanism that links BM niche damage to impaired hematopoietic recovery. These data help explain the prolonged BM hypoplasia observed in some patients and prompt further research into how other targeted therapy-based induction regimens influence the BM microenvironment.Featured ArticlesMYB activity drives emergent enhancer activation and enhancer-promoter interactions in acute lymphoblastic leukemiaRemodeling of the bone marrow vasculature induced by venetoclax and azacitidine damage

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